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Neurochemistry of RNA in Health and Disease

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (1 September 2021) | Viewed by 18639

Special Issue Editors

LMU-BioMedical Center, Department of Cellular Physiology, Ludwig-Maximilians-University of Munich, Großhaderner Str.9, 82152 Planegg-Martinsried, Germany
Interests: neuronal development; dendritogenesis; dentritic spines; synaptic plasticity; mRNA trafficking; signal transduction; neurovascular link
LMU-BioMedical Center, Department of Cell Biology, Ludwig-Maximilians-University of Munich, Großhaderner Str.9, 82152 Planegg-Martinsried, Germany
Interests: RNA-binding proteins; RNA structure; RNA translation; mRNA localization; miRNAs; post-transcriptional regulation; splicing; synaptic plasticity

Special Issue Information

Dear Colleagues,

Neurons are highly polarized cells, whose morphology strongly determines their function. This polarity is achieved and maintained by very different mechanisms, both intrinsic and extrinsic. Moreover, these mechanisms show vulnerabilities in several neurological disorders.

In recent years, special attention has been given to processes related to the regulation that lies behind the sequence and structure of key specific mRNAs. These processes regulate the expression, localization and/or RNA–protein complex formation of certain RNAs in order to achieve neuronal polarity. The aim of this Special Issue on “Neurochemistry of RNA in Health and Disease” is to present the latest advances in the field that allow us to understand and define the role of RNA chemistry and variability in the regulation of neuronal morphology and function, and how the failure of the proper function of these molecules can drive pathological conditions.

We welcome submissions about processes—such as alternative splicing, alternative 3’-UTRs, RNA post-transcriptional modifications, extracellular RNA, phase separation and local translation, among others—that contribute to neuronal polarity, from the neurogenesis process to the active processes of learning and memory formation, in both health and disease.

Original research, new methodologies and review articles will be considered for publication.

Dr. Inmaculada Segura
Dr. Sandra M. Fernandez-Moya
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mRNA processing
  • RNA modification
  • alternative splicing
  • local translation
  • phase separation
  • extracellular RNA
  • neuronal polarity
  • neurochemistry

Published Papers (4 papers)

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Research

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19 pages, 2708 KiB  
Article
The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex
by Rebecca M. Sena, Jeffery L. Twiss, Amy S. Gardiner, Michela Dell’Orco, David N. Linsenbardt and Nora I. Perrone-Bizzozero
Molecules 2021, 26(10), 2836; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26102836 - 11 May 2021
Cited by 12 | Viewed by 3045
Abstract
The neuronal Hu/ELAV-like proteins HuB, HuC and HuD are a class of RNA-binding proteins that are crucial for proper development and maintenance of the nervous system. These proteins bind to AU-rich elements (AREs) in the untranslated regions (3′-UTRs) of target mRNAs regulating mRNA [...] Read more.
The neuronal Hu/ELAV-like proteins HuB, HuC and HuD are a class of RNA-binding proteins that are crucial for proper development and maintenance of the nervous system. These proteins bind to AU-rich elements (AREs) in the untranslated regions (3′-UTRs) of target mRNAs regulating mRNA stability, transport and translation. In addition to these cytoplasmic functions, Hu proteins have been implicated in alternative splicing and alternative polyadenylation in the nucleus. The purpose of this study was to identify transcriptome-wide effects of HuD deletion on both of these nuclear events using RNA sequencing data obtained from the neocortex of Elavl4–/– (HuD KO) mice. HuD KO affected alternative splicing of 310 genes, including 17 validated HuD targets such as Cbx3, Cspp1, Snap25 and Gria2. In addition, deletion of HuD affected polyadenylation of 53 genes, with the majority of significantly altered mRNAs shifting towards usage of proximal polyadenylation signals (PAS), resulting in shorter 3′-UTRs. None of these genes overlapped with those showing alternative splicing events. Overall, HuD KO had a greater effect on alternative splicing than polyadenylation, with many of the affected genes implicated in several neuronal functions and neuropsychiatric disorders. Full article
(This article belongs to the Special Issue Neurochemistry of RNA in Health and Disease)
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Review

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24 pages, 1244 KiB  
Review
RNA Dynamics in Alzheimer’s Disease
by Agnieszka Rybak-Wolf and Mireya Plass
Molecules 2021, 26(17), 5113; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26175113 - 24 Aug 2021
Cited by 25 | Viewed by 5831
Abstract
Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder that heavily burdens healthcare systems worldwide. There is a significant requirement to understand the still unknown molecular mechanisms underlying AD. Current evidence shows that two of the major features of AD are transcriptome [...] Read more.
Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder that heavily burdens healthcare systems worldwide. There is a significant requirement to understand the still unknown molecular mechanisms underlying AD. Current evidence shows that two of the major features of AD are transcriptome dysregulation and altered function of RNA binding proteins (RBPs), both of which lead to changes in the expression of different RNA species, including microRNAs (miRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs). In this review, we will conduct a comprehensive overview of how RNA dynamics are altered in AD and how this leads to the differential expression of both short and long RNA species. We will describe how RBP expression and function are altered in AD and how this impacts the expression of different RNA species. Furthermore, we will also show how changes in the abundance of specific RNA species are linked to the pathology of AD. Full article
(This article belongs to the Special Issue Neurochemistry of RNA in Health and Disease)
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24 pages, 947 KiB  
Review
Brain Long Noncoding RNAs: Multitask Regulators of Neuronal Differentiation and Function
by Sarva Keihani, Verena Kluever and Eugenio F. Fornasiero
Molecules 2021, 26(13), 3951; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26133951 - 28 Jun 2021
Cited by 7 | Viewed by 3365
Abstract
The extraordinary cellular diversity and the complex connections established within different cells types render the nervous system of vertebrates one of the most sophisticated tissues found in living organisms. Such complexity is ensured by numerous regulatory mechanisms that provide tight spatiotemporal control, robustness [...] Read more.
The extraordinary cellular diversity and the complex connections established within different cells types render the nervous system of vertebrates one of the most sophisticated tissues found in living organisms. Such complexity is ensured by numerous regulatory mechanisms that provide tight spatiotemporal control, robustness and reliability. While the unusual abundance of long noncoding RNAs (lncRNAs) in nervous tissues was traditionally puzzling, it is becoming clear that these molecules have genuine regulatory functions in the brain and they are essential for neuronal physiology. The canonical view of RNA as predominantly a ‘coding molecule’ has been largely surpassed, together with the conception that lncRNAs only represent ‘waste material’ produced by cells as a side effect of pervasive transcription. Here we review a growing body of evidence showing that lncRNAs play key roles in several regulatory mechanisms of neurons and other brain cells. In particular, neuronal lncRNAs are crucial for orchestrating neurogenesis, for tuning neuronal differentiation and for the exact calibration of neuronal excitability. Moreover, their diversity and the association to neurodegenerative diseases render them particularly interesting as putative biomarkers for brain disease. Overall, we foresee that in the future a more systematic scrutiny of lncRNA functions will be instrumental for an exhaustive understanding of neuronal pathophysiology. Full article
(This article belongs to the Special Issue Neurochemistry of RNA in Health and Disease)
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18 pages, 1592 KiB  
Review
RNA Proximity Labeling: A New Detection Tool for RNA–Protein Interactions
by Ronja Weissinger, Lisa Heinold, Saira Akram, Ralf-Peter Jansen and Orit Hermesh
Molecules 2021, 26(8), 2270; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26082270 - 14 Apr 2021
Cited by 11 | Viewed by 5953
Abstract
Multiple cellular functions are controlled by the interaction of RNAs and proteins. Together with the RNAs they control, RNA interacting proteins form RNA protein complexes, which are considered to serve as the true regulatory units for post-transcriptional gene expression. To understand how RNAs [...] Read more.
Multiple cellular functions are controlled by the interaction of RNAs and proteins. Together with the RNAs they control, RNA interacting proteins form RNA protein complexes, which are considered to serve as the true regulatory units for post-transcriptional gene expression. To understand how RNAs are modified, transported, and regulated therefore requires specific knowledge of their interaction partners. To this end, multiple techniques have been developed to characterize the interaction between RNAs and proteins. In this review, we briefly summarize the common methods to study RNA–protein interaction including crosslinking and immunoprecipitation (CLIP), and aptamer- or antisense oligonucleotide-based RNA affinity purification. Following this, we focus on in vivo proximity labeling to study RNA–protein interactions. In proximity labeling, a labeling enzyme like ascorbate peroxidase or biotin ligase is targeted to specific RNAs, RNA-binding proteins, or even cellular compartments and uses biotin to label the proteins and RNAs in its vicinity. The tagged molecules are then enriched and analyzed by mass spectrometry or RNA-Seq. We highlight the latest studies that exemplify the strength of this approach for the characterization of RNA protein complexes and distribution of RNAs in vivo. Full article
(This article belongs to the Special Issue Neurochemistry of RNA in Health and Disease)
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